DESCRIPTION (Modified from applicant's abstract) In nerve cells, regulated local synthesis in dendrites of a number of key postsynaptic proteins may be of critical relevance for the long-term structural and functional plasticity of synaptic connections. An essential prerequisite for such a mechanism is the targeted transport of select RNAs to dendritic sites of translation. The notion of specific RNA transport in dendrites has gained support by the recent observation in the applicant's lab that a cis-acting signaling element that is contained with a dendritic RNA is responsible for the targeting of the RNA to dendrites. Based on these data, the central objectives of this research project are defined as the dissection of RNA transport mechanisms in dendrites and the analysis of feedback mechanisms that would allow the local regulation of dendritic RNA transport through physiological events at the synapse. In Specific Aim 1 it is planned to define, in terms of primary and/or higher order structure, the physical fine structure of minimal essential targeting module(s). In the Second Aim, it will be established whether and how transport of dendritic RNAs is regulated through neuronal activity. Under this Specific Aim is the question of what mechanisms are being used by neurons to modulate the diversity of dendritic proteins in response to functional input at the synapse. The overall goal of this research project is thus to ascertain the functional significance of dendritic RNA transport mechanisms that are likely to be of vital importance in the regulation of mosaic postsynaptic protein repertoires, and thus for the development and long-term plasticity of synaptic connections between nerve cells.